Beta-Lactams: Penicillins and Cephalosporins
Mechanism: inhibit transpeptidase (penicillin-binding proteins), preventing peptidoglycan cross-linking. Penicillin G: strep, syphilis, meningococcus, actinomyces. Amoxicillin-clavulanate: adds beta-lactamase coverage (MSSA, H. influenzae, Moraxella). Cephalosporins by generation: 1st (cefazolin) = MSSA/strep, surgical prophylaxis; 3rd (ceftriaxone) = gram-negatives, N. gonorrhoeae, meningitis; 4th (cefepime) = Pseudomonas; 5th (ceftaroline) = MRSA coverage.
Carbapenems and the Gram-Negative Heavyweights
Carbapenems (imipenem, meropenem, ertapenem): broadest beta-lactam coverage — ESBL-producing gram-negatives, anaerobes, most gram-positives except MRSA. Note: ertapenem does NOT cover Pseudomonas or Acinetobacter. Aztreonam: gram-negatives only, safe in true penicillin allergy. Aminoglycosides (gentamicin, tobramycin): synergy for gram-negatives including Pseudomonas, ototoxicity/nephrotoxicity.
MRSA Coverage: When to Use It
MRSA-active agents: Vancomycin (gold standard for serious MRSA — monitor troughs, nephrotoxic), Daptomycin (gram-positive only, do NOT use for pulmonary infection — inactivated by surfactant), Linezolid (bacteriostatic, serotonin syndrome risk with SSRIs), Ceftaroline (5th-gen cephalosporin with MRSA activity), TMP-SMX (oral MRSA for skin/soft tissue). Mnemonic: 'Very Distinguished Lawyers Can't Testify' — Vancomycin, Daptomycin, Linezolid, Ceftaroline, TMP-SMX.
Macrolides, Fluoroquinolones, and Atypical Coverage
Atypicals (Mycoplasma, Legionella, Chlamydia — no cell wall, no coverage by beta-lactams): treat with macrolides (azithromycin, clarithromycin), doxycycline, or respiratory fluoroquinolones (levofloxacin, moxifloxacin). Community-acquired pneumonia: azithromycin or doxycycline (outpatient) + beta-lactam (if severe, for dual coverage). Metronidazole: anaerobes below the diaphragm, C. diff (PO for mild), bacterial vaginosis.